Thee present invention relates to a carbon dioxide-containing viscous composition which is capable of treating or ameliorating itching accompanying mucocutaneous diseases or mucocutaneous disorders such as athlete""s foot, insect bite, atopic dermatitis, nummular eczema, xeroderma, seborrheic eczema, urticaria, prurigo, housewives"" eczema, acne vulgaris, impetigo, folliculitis, carbuncle, furunculosis, phlegmon, pyoderma, psoriasis, ichthyosis, palmoplantar keratoderma, lichen, pityriasis, wound, burn, rhagades, erosion and chilblain; mucocutaneous injuries such as decubitus ulcer, wound, burn, angular stomatitis, stomatitis, skin ulcer, rhagades, erosion, chilblain and gangrene; incomplete takes of skin graft, skin flap, etc.; dental diseases such as gingivitis, alveolar pyorrhea, denture ulcer, nigricans gingiva, stomatitis; skin ulcer, cryesthesia and numbness caused by peripheral circulatory disorders such as thromboangitis obliterans, arteriolosclerosis obliterans, diabetic peripheral circulatory disorder and varicosis in lower extremity; musculoskeletal diseases such as chronic rheumatoid arthritis, cervico-omo-brachial syndrome, myalgia, arthralgia and lumbago; nervous system diseases such as neuralgia, polyarthritis and subcute myelo-optic neuropathy; keratoses such as psoriasis, corn, callosity, ichthyosis, palmoplantar keratoderma, lichen and pityriasis; suppurative dermopathies such as acne vulgaris, impetigo, folliculitis, carbuncle, furunculosis, phlegmon, pyoderma and suppurative eczema; constipation caused by loss of reflection of defecation; suppression of hair re-growth after depilation (treatment of unwanted hair); cosmetic troubles in the skin or hair such as freckles, rough skin, muddy complexion, faded skin complexion and loss of hair glossiness, etc. with little side effects as well as of slimming a desired part of the body, and to prophylactic and therapeutic methods using the composition.
Antihistamines and antiallergics for external application are typically used in a topical therapy for itching. Such drugs are used when itching occurs and work to suppress the itching temporarily to a certain degree. Itching associated with eczema is generally treated with non-steroidal anti-inflammatory drugs or steroidal drugs for external application which prevent the itching by suppressing inflammation.
However, the antihistamines and antiallergics for external application are barely effective in treating itching accompanying atopic dermatitis, athlete""s foot and insect bite. The non-steroidal anti-inflammatory drugs and steroidal drugs for external application do not effect satisfactorily nor immediately on itching. Further, the steroidal drugs are difficult to use because of the serious side effects.
The present invention provides a preparation effective for the treatment of itching accompanying mucocutaneous diseases or mucocutaneous disorders such as athlete""s foot, insect bite, atopic dermatitis, nummular eczema, xeroderma, seborrheic eczema, urticaria, prurigo, housewives"" eczema, acne vulgaris, impetigo, folliculitis, carbuncle, furunculosis, phlegmon, pyoderma, psoriasis, ichthyosis, palmoplantar keratoderma, lichen, pityriasis, wound, burn, rhagades, erosion and chilblain and therapeutic and prophylactic methods using the preparation.
Further, the invention provides a preparation effective for the treatment of mucocutaneous injuries such as decubitus ulcer, wound, burn, angular stomatitis, stomatitis, skin ulcer, rhagades, erosion, chilblain and gangrene; incomplete takes of skin graft, skin flap, etc.; dental diseases such as gingivitis, alveolar pyorrhea, denture ulcer, nigricans gingiva, stomatitis; skin ulcer, cryesthesia and numbness caused by peripheral circulatory disorders such as thromboangitis obliterans, arteriolosclerosis obliterans, diabetic peripheral circulatory disorder and varicosis in lower extremity; musculoskeletal diseases such as chronic rheumatoid arthritis, cervico-omo-brachial syndrome, myalgia, arthralgia and lumbago: nervous system diseases such as neuralgia, polyarthritis and subcute myelo-optic neuropathy; keratoses such as psoriasis, corn, callosity, ichthyosis, palmoplantar keratoderma, lichen and pityriasis; suppurative dermopathies such as acne vulgaris, impetigo, folliculitis, carbuncle, furunculosis, phlegmon, pyoderma and suppurative eczema; constipation caused by loss of reflection of defecation; suppression of hair re-growth after depilation (treatment of unwanted hair); cosmetic troubles in the skin or hair such as freckles, rough skin, muddy complexion, faded skin complexion, loss of hair glossiness, etc. and partial obesity, and prophylactic and therapeutic methods using the preparation.
The inventors accomplished the present invention as a result of an extensive research wherein they found that a carbon dioxide-containing viscous composition is effective in treating itching which had not been cured by antihistamines, anti-allergics, non-steroidal anti-inflammatory drugs, steroidal drugs for external application or the like and that the composition has an anti-inflammatory action, wound healing accelerating action, skin treatment action, action for resolving partial obesity, transdermal or transmucosal drug absorption promoting action and the like.
The invention relates to the following items 1-48.
1. A carbon dioxide-containing viscous composition comprising an aqueous viscous composition containing one or more thickeners and carbon dioxide, wherein the aqueous viscous composition comprises the carbon dioxide in the form of bubbles.
2. The carbon dioxide-containing viscous composition according to item 1, which is characterized in that the thickener comprises one or more selected from the group consisting of natural polymers, semi-synthetic polymers, synthetic polymers and inorganic substances.
3. The carbon dioxide-containing viscous composition according to item 1 or 2, which is characterized in that the natural polymer used as a thickener is at least one selected from the group consisting of gum arabic, carrageenan, galactan, agar, quince seed gum, guar gum, tragacanth gum, pectin, mannan, locust bean gum, wheat starch, rice starch, corn starch, potato starch, curdlan, xanthan gum, succinoglucan, dextran, hyaluronic acid, pullulan, albumin, casein, collagen, gelatin and fibroin; the semi-synthetic polymer used as a thickener is at least one selected from the group consisting of ethyl cellulose, carboxymethyl cellulose and salts thereof, carboxymethylethyl cellulose and salts thereof, carboxymethyl starch and salts thereof, croscarmellose and salts thereof, crystalline cellulose, cellulose acetate, cellulose acetate phthalate, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, hydroxypropylmethyl cellulose phthalate, powdered cellulose, methyl cellulose, methylhydroxypropyl cellulose, pregelatinized starch, partially pregelatinized starch, carboxymethyl starch, dextrin, methyl starch, sodium alginate, propyleneglycol alginate, sodium chondroitin sulfate and sodium hyaluronate; the synthetic polymer used as a thickener is at least one selected from the group consisting of carboxyvinyl polymer, sodium polyacrylate, polyvinylacetaldiethylaminoacetate, polyvinyl alcohol, polyvinyl pyrrolidone, methacrylic acid-ethyl acrylate copolymer, methacrylic acid-ethyl methacrylate copolymer, ethyl methacrylate.trimethylammoniumethyl chloride methacrylate copolymer, dimethylaminoethyl methacrylate.methyl methacrylate copolymer; the inorganic substance used as a thickener is at least one selected from the group consisting of silicon dioxide hydrate, light anhydrous silicic acid, colloidal alumina, bentonite and laponite.
4. The carbon dioxide-containing viscous composition according to any one of items 1-3, which is characterized in that the carbon dioxide is produced by reacting an acid or acids with a carbonate or carbonates.
5. The carbon dioxide-containing viscous composition according to item 4, which is characterized in that the acid is at least one selected from the group consisting of formic acid, acetic acid, propionic acid, butyric acid, valeric acid, oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, fumaric acid, maleic acid, phthalic acid, isophthalic acid, terephthalic acid, glutamic acid, asparagic acid, glycolic acid, malic acid, tartaric acid, citric acid, lactic acid, hydroxyacrylic acid, xcex1-oxybutric acid, glyceric acid, tartronic acid, salicylic acid, gallic acid, tropic acid, ascorbic acid, gluconic acid, phosphoric acid, potassium dihydrogenphosphate, sodium dihydrogenphosphate, sodium sulfite, potassium sulfite, sodium pyrosulfite, potassium pyrosulfite, acid sodium hexamethaphosphate, acid potassium hexamethaphosphate, acid sodium pyrophosphate, acid potassium pyrophosphate and sulfamic acid; and the carbonate is at least one selected from the group consisting of ammonium carbonate, potassium carbonate, calcium carbonate, sodium carbonate, sodium bicarbonate, potassium bicarbonate, potassium sesquicarbonate, calcium sesquicarbonate and sodium sesquicarbonate.
6. A kit comprising a carbonate or carbonates, an acid or acids, a thickener or thickeners and water in a state where the components produce substantially no carbon dioxide, which enables to produce a carbon dioxide-containing viscous composition comprising carbon dioxide bubbles by mixing the carbonate or carbonates, the acid or acids, the thickener or thickeners and water.
7. The kit according to item 6, comprising a carbonate-containing aqueous viscous composition and an acid or acids.
8. The kit according to item 6, comprising an acid-containing aqueous viscous composition and a carbonate or carbonates.
9. The kit according to item 6, comprising a carbonate-containing aqueous viscous composition and a granular (fine-granular or powdery) acid or acids.
10. The kit according to item 6, comprising an acid-containing aqueous viscous composition and a granular (fine-granular or powdery) carbonate or carbonates.
11. The kit according to item 6, comprising a carbonate-containing aqueous viscous composition and an acid-containing aqueous viscous composition.
12. The kit according to item 6, comprising a composite granule (fine-granular or powdery) of a carbonate or carbonates and an acid or acids and an aqueous viscous composition.
13. The kit according to item 6, comprising a carbonate-containing aqueous viscous composition and an acid-containing sheet.
14. The kit according to item 6, comprising an acid-containing aqueous viscous composition and a carbonate-containing sheet.
15. The kit according to item 6, comprising a carbonate or carbonates, an acid or acids and aqueous viscous composition.
16. The kit according to item 6, comprising an aqueous viscous composition and sheet containing a composite granule (fine-granular or powdery) of carbonate and acid.
17. The kit according to item 6, comprising a carbonate or carbonates, an acid or acids, a thickener or thickeners and water.
18. A pharmaceutical composition comprising, as an active ingredient, the carbon dioxide-containing viscous composition according to any one of items 1-5 or the carbon dioxide-containing viscous composition obtainable by the kit according to any one of items 6-17.
19. The pharmaceutical composition according to item 18, which is a prophylactic or therapeutic drug for itching accompanying mucocutaneous diseases or mucocutaneous disorders.
20. The pharmaceutical composition according to item 18, which is a prophylactic or therapeutic drug for skin ulcer, cryesthesia and numbness caused by peripheral circulatory disorders.
21. The pharmaceutical composition according to item 18, which is a prophylactic or therapeutic drug for dental diseases.
22. The pharmaceutical composition according to item 18, which is a prophylactic or therapeutic drug for mucocutaneous injuries.
23. The pharmaceutical composition according to item 18, which is a prophylactic or therapeutic drug for suppurative dermopathies.
24. The pharmaceutical composition according to item 18, which is a prophylactic or therapeutic drug for keratosis.
25. The pharmaceutical composition according to item 18, which is a prophylactic or therapeutic drug for musculoskeletal diseases.
26. The pharmaceutical composition according to item 18, which is a prophylactic or therapeutic drug for nervous system diseases.
27. Cosmetics comprising the carbon dioxide-containing viscous composition according to any one of items 1-5 or the carbon dioxide-containing viscous composition obtainable by the kit according to any one of items 6-17.
28. The cosmetics according to item 27, being capable of reducing or attenuating freckles.
29. Slimming cosmetics according to item 27, being capable of ameliorating partial obesities in the face, foot, arm, abdomen, latus, back, neck, chin and the like.
30. The cosmetics according to item 27, having an action of ameliorating skin complexion.
31. The cosmetics according to item 27, having an action of suppressing hair re-growth after depilation.
32. A prophylactic or therapeutic method for diseases or disorders, comprising applying to a patient an effective amount of the carbon dioxide-containing viscous composition according to any one of items 1-5 or the carbon dioxide-containing viscous compositions obtainable by the kit according to any one of items 6-17.
33. The prophylactic or therapeutic method according to item 32, wherein the diseases or disorders are mucocutaneous diseases or mucocutaneous disorders accompanied by itching.
34. The prophylactic or therapeutic method according to item 33, wherein the mucocutaneous diseases or mucocutaneous disorders accompanied by itching are athlete""s foot, insect bite, atopic dermatitis, nummular eczema, xeroderma, seborrheic eczema, urticaria, prurigo, housewives"" eczema, acne vulgaris, impetigo, folliculitis, carbuncle, furunculosis, phlegmon, pyoderma, psoriasis, ichthyosis, palmoplantar keratoderma, lichen, pityriasis, wound, burn, chilblain, rhagades and erosion.
35. The prophylactic or therapeutic method according to item 32, wherein the diseases or disorders are mucocutaneous injuries.
36. The prophylactic or therapeutic method according to item 35, wherein the mucocutaneous injuries are decubitus ulcer, wound, burn, angular stomatitis, stomatitis, skin ulcer, rhagades, erosion, chilblain and gangrene.
37. The prophylactic or therapeutic method according to item 32, wherein the diseases or disorders are suppurative dermopathies.
38. The prophylactic or therapeutic method according to item 37, wherein the suppurative dermopathies are acne vulgaris, impetigo, folliculitis, carbuncle, furunculosis, phlegmon, pyoderma and suppurative eczema.
39. The prophylactic or therapeutic method according to item 32, wherein the diseases or disorders are keratoses.
40. The prophylactic or therapeutic method according to item 39, wherein the keratoses are psoriasis, corn, callosity, ichthyosis, palmoplantar keratoderma, lichen and pityriasis.
41. The prophylactic or therapeutic method according to item 32, wherein the diseases or disorders are musculoskeletal diseases.
42. The prophylactic or therapeutic method according to item 41, wherein the musculoskeletal diseases are chronic rheumatoid arthritis, cervico-omo-brachial syndrome, myalgia, arthralgia and lumbago.
43. The prophylactic or therapeutic method according to item 32, wherein the diseases or disorders are dental diseases.
44. The prophylactic or therapeutic method according to item 43, wherein the dental diseases are gingivitis, alveolar pyorrhea, denture ulcer, nigricans gingiva and stomatitis.
45. The method for the prevention or treatment according to item 32, wherein the diseases or disorders are nervous system diseases.
46. The prophylactic or therapeutic method according to item 45, wherein the nervous system disease are neuralgia, polyarthritis and subcute myelo-optic neuropathy.
47. The prophylactic or therapeutic method according to item 32, wherein the diseases or disorders are skin ulcer, cryesthesia and numbness caused by peripheral circulatory disorders.
48. The prophylactic or therapeutic method according to item 47, wherein the peripheral circulatory disorders are thromboangitis obliterans, arteriolosclerosis obliterans, diabetic peripheral circulatory disorder and varicosis in lower extremity.
Examples of the mucocutaneous diseases or mucocutaneous disorders accompanied by itching are athlete""s foot, insect bite, atopic dermatitis, nummular eczema, xeroderma, seborrheic eczema, urticaria, prurigo, housewives"" eczema, acne vulgaris, impetigo, folliculitis, carbuncle, furunculosis, phlegmon, pyoderma, psoriasis, ichthyosis, palmoplantar keratoderma, lichen, pityriasis, wound, burn, rhagades, erosion, chilblain and the like.
Examples of the mucocutaneous injuries are decubitus ulcer, wound, burn, angular stomatitis, stomatitis, skin ulcer, rhagades, erosion, chilblain, gangrene and the like.
Examples of the suppurative dermopathies are acne vulgaris, impetigo, folliculitis, carbuncle, furunculosis, phlegmon, pyoderma, suppurative eczema and the like.
Examples of the keratoses are psoriasis, corn, callosity, ichthyosis, palmoplantar keratoderma, lichen, pityriasis and the like.
Examples of the musculoskeletal diseases are chronic rheumatoid arthritis, cervico-omo-brachial syndrome, myalgia, arthralgia, lumbago and the like.
Examples of the dental diseases are gingivitis, alveolar pyorrhea, denture ulcer, nigricans gingiva, stomatitis and the like.
Examples of the peripheral circulatory disorders which cause skin ulcer, cryesthesia and numbness are thromboangitis obliterans, arteriolosclerosis obliterans, diabetic peripheral circulatory disorder, varicosis in lower extremity and the like.
Examples of the nervous system diseases are neuralgia, polyarthritis, subcute myelo-optic neuropathy and the like.
The cosmetics have various actions of whitening, ameliorating skin complexion, ameliorating freckles, partial slimming, suppressing hair re-growth after depilation, ameliorating glossiness of hair and the like, and may be used in the form of cream, gel, paste, cleansing foam, face pack, face mask and the like.
The xe2x80x9caqueous viscous compositionxe2x80x9d of the present invention is a composition containing one or more thickeners dissolved in water or swollen with water. The composition is capable of retaining carbon dioxide bubbles in such a volume that carbon dioxide is supplied to the subcutaneous tissue and so on when the composition is applied to the mucocutaneous or injured skin tissue. The composition to be used is not limited as long as it can retain carbon dioxide in the form of bubbles. The composition may contain any thickeners which are used for conventional pharmaceutical preparations, cosmetics, foods and the like without limitation, and the dosage form thereof may be any one of those typically applied for treating the mucocutaneous or injured tissue, hair, etc. such as gel, cream, paste, mousse or the like.
The present invention includes, for example, the following kits:
1) a kit comprising a carbonate-containing aqueous viscous composition and acid;
2) a kit comprising an acid-containing aqueous viscous composition and carbonate;
3) a kit comprising a carbonate-containing aqueous viscous composition and granular (fine-granular or powdery) acid;
4) a kit comprising an acid-containing aqueous viscous composition and granular (fine-granular or powdery) carbonate;
5) a kit comprising a carbonate-containing aqueous viscous composition and acid-containing aqueous viscous composition;
6) a kit comprising a composite granule (fine-granule or powder) of carbonate and acid and aqueous viscous composition;
7) a kit comprising a carbonate-containing aqueous viscous composition and acid-containing sheet;
8) a kit comprising an acid-containing aqueous viscous composition and carbonate-containing sheet;
9) a kit comprising a carbonate, acid and aqueous viscous composition;
10) a kit comprising an aqueous viscous composition and sheet containing the composite granule (fine-granule or powder) of carbonate and acid; and
11) a kit comprising a carbonate, acid, water and thickener.
The composition of the present invention containing carbon dioxide bubbles can be produced by mixing the components comprised in any one of the kits before use.
As the thickener, a natural polymer, semi-synthetic polymer, synthetic polymer, inorganic substance or the like, for example, may be used alone or in combination of two or more.
The natural polymer may be, for example, a plant-derived polymer, microorganism-derived polymer and proteinaceous polymer.
The semi-synthetic polymer may be, for example, a cellulosic polymer, starch polymer, alginate polymer and other polysaccharide polymers.
Examples of the plant-derived polymer included in the natural polymer to be used as a thickener in the invention are gum arabic, carrageenan, galactan, agar, quince seed gum, guar gum, tragacanth gum, pectin, mannan, locust bean gum, wheat starch, rice starch, corn starch, potato starch and the like.
Examples of the microorganism-derived polymer included in the natural polymer to be used as a thickener in the invention are curdlan, xanthan gum, succinoglucan, dextran, hyaluronic acid, pullulan and the like.
Examples of the proteinaceous polymer included in the natural polymer to be used as a thickener in the invention are albumin, casein, collagen, gelatin, fibroin and the like.
Examples of the cellulosic polymer included in the semi-synthetic polymer to be used as a thickener in the invention are ethyl cellulose, carboxymethyl cellulose and salts thereof, carboxymethylethyl cellulose and salts thereof, carboxymethyl starch and salts thereof, croscarmellose and salts thereof, crystalline cellulose, cellulose acetate, cellulose acetate phthalate, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, hydroxypropylmethyl cellulose phthalate, powdered cellulose, methyl cellulose, methylhydroxypropyl cellulose and the like.
Examples of the starch polymer included in the semi-synthetic polymer to be used as a thickener in the invention are pregelatinized starch, partially pregelatinized starch, carboxymethyl starch, dextrin, methyl starch and the like.
Examples of the alginate polymer included in the semi-synthetic polymer to be used as a thickener in the invention are sodium alginate, propyleneglycol alginate and the like.
Examples of the other polysaccharides polymers included in the semi-synthetic polymer to be used as a thickener in the invention are sodium chondroitin sulfate and sodium hyaluronate and the like.
Examples of the synthetic polymer to be used as a thickener in the invention are carboxyvinyl polymer, sodium polyacrylate, polyvinylacetaldiethylaminoacetate, polyvinyl alcohol, polyvinyl pyrrolidone, methacrylic acid-ethyl acrylate copolymer, methacrylic acid-ethyl methacrylate copolymer, ethyl methacrylate.trimethylammoniumethyl chloride methacrylate copolymer, dimethylaminoethyl methacrylate.methyl methacrylate copolymer and the like.
Examples of the inorganic substance to be used as a thickener in the invention are silicon dioxide hydrate, light anhydrous silicic acid, colloidal alumina, bentonite, laponite and the like.
The carbon dioxide may be retained in the aqueous composition of the invention by means of a carbon dioxide gas bomb or the like, for example, wherein carbon dioxide is introduced directly to the composition.
In addition, it is possible to obtain the carbon dioxide-containing viscous composition by reacting substances, which produce carbon dioxide as a result of the reaction, in an aqueous viscous composition or by generating carbon dioxide at the same time with forming an aqueous viscous composition. The substances to generate carbon dioxide may be a carbonate and acid used in combination. Specifically, the following combinations can produce the viscous composition containing carbon dioxide; however, the present invention is not limited thereto and other combinations may be used as long as they are capable of forming the viscous composition retaining carbon dioxide in the form of bubbles.
1) a combination of a carbonate-containing aqueous viscous composition and acid;
2) a combination of an acid-containing aqueous viscous composition and carbonate;
3) a combination of a carbonate-containing aqueous viscous composition and granular (fine-granular or powdery) acid;
4) a combination of an acid-containing aqueous viscous composition and granular (fine-granular or powdery) carbonate;
5) a combination of a carbonate-containing aqueous viscous composition and acid-containing aqueous viscous composition;
6) a combination of a composite granule (fine-granule or powder) of carbonate and acid and aqueous viscous composition;
7) a combination of a carbonate-containing aqueous viscous composition and acid-containing sheet;
8) a combination of an acid-containing aqueous viscous composition and carbonate-containing sheet;
9) a combination of a carbonate, acid and aqueous viscous composition;
10) a combination of an aqueous viscous composition and sheet containing the composite granule (fine-granule or powder) of carbonate and acid; and
11) a combination of a carbonate, acid, water and thickener.
In addition, the carbonate-containing aqueous viscous composition, acid-containing aqueous viscous composition and aqueous viscous composition may respectively be prepared from a preparation such as a thickener-containing granular (fine-granular or powdery) carbonate or the like, a thickener-containing granular (fine-granular or powdery) acid or the like and a thickener-containing granule (fine-granule or powder) or the like. If the thickener-containing granular (fine-granular or powdery) carbonate or the like and the thickener-containing granular (fine-granular or powdery) acid or the like are prepared to be controlled-release preparations of a carbonate and acid, the prolonged action of the composition can be intensified.
The carbonate to be used in the invention may be one or more of ammonium carbonate, potassium carbonate, calcium carbonate, sodium carbonate, sodium bicarbonate, potassium sesquicarbonate, calcium sesquicarbonate and sodium sesquicarbonate and potassium bicarbonate.
The acid to be used in the invention may be either of organic acid or inorganic acid, which are used alone or in combination of two or more.
Examples of the organic acid are straight chain fatty acids such as formic acid, acetic acid, propionic acid, butyric acid and valeric acid; dicarboxylic acid such as oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, fumaric acid, maleic acid, phthalic acid, isophthalic acid, terephthalic acid; acidic amino acid such as glutamic acid and asparagic acid; oxy-acid such as glycolic acid, malic acid, tartaric acid, citric acid, lactic acid, hydroxyacrylic acid, xcex1-oxybutric acid, glyceric acid, tartronic acid, salicylic acid, gallic acid, tropic acid, ascorbic acid and gluconic acid, etc.
Examples of the inorganic acid are phosphoric acid, potassium dihydrogenphosphate, sodium dihydrogenphosphate, sodium sulfite, potassium sulfite, sodium pyrosulfite, potassium pyrosulfite, acid sodium hexamethaphosphate, acid potassium hexamethaphosphate, acid sodium pyrophosphate, acid potassium pyrophosphate, sulfamic acid and the like.
Various medicinal substances such as a bactericide, antibiotics, fungicide, anti-inflammatory drug, hemostat, local anesthetic, wound-healing accelerating agent, vasodilator, fibrinolytic, keratolytic, moisturizer, various vitamins, various hormones, antipruritic and hair root activating agent may be added to the compositions of the invention to intensify the effect or to produce synergy.
It is possible to improve the skin comfort, usability and the like of the composition by adding a perfume, color material, moisturizer, oily component, surfactant, etc. and preparing the compositions in the dosage form of a cream, gel, paste, cleansing foam, face pack, face mask or the like. The perfume to be used may be one or more of a natural perfume, synthetic perfume, mixed perfume and the like.
Examples of the natural perfume are vegetable perfumes such as a rose oil, jasmine oil, neroli oil, lavender oil, ylang-ylang oil, tuberose oil, clary sage oil, clove oil, peppermint oil, geranium oil, patchouli oil, sandalwood oil, cinnamon oil, coriander oil, nutmeg oil, pepper oil, lemon oil, orange oil, bergamot oil, opoponax oil, vetiver oil, orris oil and oakmoss oil and animal oils such as a musk oil, civet oil, castoreum oil and ambergris oil.
Examples of the synthetic perfume are hydrocarbons such as limonene and xcex2-caryophyllene; alcohols such as santalol, cis-3-hexenol, linalol, geraniol, citronellal, terpineol, bacdanol, farnesol, xcex2-phenylethylalcohol, bramanol and menthol; aldehydes such as 2,6-nonadienal, citral, xcex1-hexyl cinnamic aldehyde, lyral and lilial; ketones such as acetylcedrene, xcex2-ionone, Iso E Super, irones, l-carbone, cyclopentadecanone, damascone, methyl ionones and muscone; esters such as benzylacetate, methyl dihydrojasmonate, methyl jasmonate and linalyl acetate; lactones such as xcex2-undecalactone, jasminelactone, cyclopentadecanolide and ethylene brassylate; oxides such as anbroxane, galaxolide and rose oxide; nitrogen-containing compounds such as indole; acetals such as phenylacetaldehyde dimethylacetal; Schiff""s bases such as aurantiol and the like.
Examples of the mixed perfume are animal, aldehyde, woody, oriental, citrus, chypre, spicy, green, fougere, floral, fruity and the like.
As a coloring material, an organic artificial dye, natural dye, inorganic pigment and polymer powder may be used alone or in combination of two or more.
Examples of the organic artificial dye are red dyes such as Amaranth, Erythrosine, New Coccine, Phloxine B, Rose Bengal, Acid Red, Lithol Rubin B, Lake Red, Lithol Red, Rhodamine B, Tetrachrome Tetrabromo, Brilliant Lake Red R, Deep Maroon, Toluidine Red, Tetrabromo Fluorescein, Sudan III, Helindon Pink, Fast Acid Magenta, Parmaton Red, Eosine YS, Phloxine BK, Violamine R, Brilliant Fast Scarlet, Ponceau R, Oil Red XO and Fast Red S; yellow dyes such as Tartrazine, Sunset Yellow FCF, Fluorescein, Uranine, Hansa Yellow, Pola Yellow 5G, Naphthol Yellow S, Yellow AB, Methanyl Yellow and Fast Light Yellow 3G; green dyes such as Fast Green FCF, Alizarin Cyanine Green, Quinizarin Green SS, Pyraninconque, Light Green SF Yellow, Naphthol Green B and Guinea Green B; blue dyes such as Brilliant Blue FCF, Indigo Carmine, Indigo, Patent Blue NA, Carbanthrene Blue, Alphazurine FG, Sudan Blue and Phthalo Cyanine Blue; orange dyes such as Dibromofluorescein, Permanent Orange, Benzin Orange G, Orange II, Diuodofluoresceine, Erythrosine yellow NA, Hansa Orange and Orange SS; brown dyes such as Resorcin Brown; violet dyes such as Alisarine purple and Arisrol Purple; and black dyes such as Naphtho Blue Black; etc.
Examples of the natural dye are carotenoid-based colorants such as xcex2-carotene, xcex2-apo-8-carotenal, capsanthin, liropin, bixin, crocin and canthaxantin; flavonoid-based colorants such as shisonin, rafanin, ninocyanine, carthamin, sufrole yellow, rutin, quercetin and cacao dye; flavine-based colorants such as liboflavine; quinone-based colorants such as laccaic acid, carminic acid, kermesic acid, alizarin, shikonin, arcanine, nichinochrome; porphyrin-based colorants such as chlorophyll and hemoglobin; diketon-based colorants such as curcumine; and betacyanizine-based dyes such as betanin; etc.
Examples of the inorganic pigment are fillers such as mica, talc, kaolin, calcium carbonate, magnesium carbonate, silicic acid anhydride, aluminium oxide and barium sulfate; coloring pigments such as red iron oxide, yellow iron oxide, black iron oxide, chromium oxide, ultramarine, iron blue and carbon black; white pigments such as titanium dioxide and zinc oxide; pearly pigments such as titanated mica, fish scale flake and bismuth oxichloride; and particularly functioning pigments such as boron nitride, photochromic pigments, synthetic fluorine gold mica and iron containing synthetic fluorine gold mica; etc.
Examples of the polymer powder are polyethylene powder, poly(methyl methacrylate), polyethylenetelephthalate.polymethylmethacrylate laminate powder, nylon powder and the like.
Examples of the moisturizer are sorbitol, glycerin, sodium lactate, sodium hyaluronate, sodium 2-pirrolydone-5-carboxylate, 1,3-butylene glycol, propylene glycol, polyethylene glycol and the like.
Examples of the oily component are oils and fats such as avocado oil, almond oil, olive oil, cacao butter, hardened palm oil, synthetic triglyceride, evening primrose oil, castor oil, sunflower oil, jojoba oil and macadamian nut oil; hydrocarbons such as squalane, ceresin, hard paraffin, microcrystalline wax, liquid paraffin and vaseline; waxes such as carnauba wax, candelilla wax, yellow bees wax and lanolin; higher alcohols such as isostearyl alcohol, 2-octyldodecanol, stearyl alcohol, cetyl alcohol, cholesterol, hexadecyl alcohol and behenyl alcohol; fatty acids such as isostearic acid, oleic acid, stearic acid, parmitic acid, behenic acid and myristic acid; synthetic esters such as isopropylmyristate, cetyl 2-ethylhexanoate, glycerin triester, cholesteryl ester, pentaerythritol tetraester, diisosteryl malate; and silicone oils such as cyclomethicon, dimethyl polysiloxane, methyl polysiloxane and methyphenyl polysiloxane; etc.
Examples of the surfactant are nonionic surfactants such as diglycerol dioleate, sorbitan fatty acid ester, glycerin monooleate, glycerin monostearate, propyleneglycol monostearate, polyoxyethylene alkylether, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene.polyoxypropylene block polymer, polyoxyethylen hydrogenated castor oil; anionic surfactants such as acyl-N-methyltaurine salt, salt of alkylether phosphate ester, alkyl sodium sulfate, N-acyl-amino acid salt, higher fatty acid soap and polyoxyethylene alkylether sulfate; etc.
In the case of using the carbon dioxide-containing viscous composition of the invention for the therapy or prophylaxis of mucocutaneous diseases or mucocutaneous disorders or for the cosmetic purpose, the composition may be applied to a part of the body directly, by using an absorbent material such as a gauze or sponge or by patching a bag made of the absorbent material wherein the composition is filled. More enhanced efficacy is provided by employing a closure therapy in combination with the above-mentioned therapy or prophylaxis, wherein the part of the body to which the composition is applied is covered with a film of poor permeability or dressing material. It is also efficacious to bathe a part of the body in a vessel charged with the composition. In this case, prolonged efficacy is provided by resupplying carbon dioxide to the composition by using a carbon dioxide bomb or the like.
In the case of using the carbon dioxide-containing viscous composition of the invention for treating constipation, the composition may be injected to the rectum by means of a tube or syringe as is the case with an enema.
In the case of using the carbon dioxide-containing viscous composition of the invention for the treatment of stomatitis or the like, the composition may be used as a gurgle in addition to the same usage as that described in the therapy or prophylaxis of mucocutaneous diseases or mucocutaneous disorders or for the cosmetic purpose.
In the case of using the carbon dioxide-containing viscous composition of the invention for dental diseases, the composition may be administered to the periodontal pocket using a syringe or the like in treating periodontal diseases. More enhanced efficacy is provided by covering the gum around the periodontal pocket with the composition. When the composition is used for treating stomatitis or nigricans gingiva, the affected area may be covered with the composition using a syringe or spatula. When treating denture ulcer, the composition may be applied to the ulcer in an appropriate amount to cover the affected area. Satisfactory efficacy can be provided even if a denture is attached to the gum after covering the ulcer with the composition.
The carbon dioxide-containing viscous composition of the invention can be removed easily by wiping with a tissue paper, etc. or washing with water, etc. However, materials used for the composition and the composition itself are highly safety. Therefore, in a case where the composition is administered for treating the injured tissue such as decubitus ulcer, etc., no trouble will be caused even if the composition is not removed completely from the affected area. As the case may be, the composition can be applied to the affected area without removing the composition applied previously.
In the case of using the carbon dioxide-containing viscous composition of the invention for the purpose of partial slimming, the composition may be applied to the abdomen or the like when taking a bath so that the composition can be easily washed away after a predetermined time.
The carbon dioxide-containing viscous composition of the invention is effective for a therapy or prophylaxis of itching, various mucocutaneous diseases or mucocutaneous disorders or when used for the cosmetic purpose even if it is removed after being applied to the skin or mucosa for a few minutes. However, the composition is typically applied to the skin and mucosa or the injured tissue of the skin for 5 minutes or more. The composition is also effective in saving labor required for ministration, especially in treating decubitus ulcer, since the composition can be used continuously for 24 hours or more. When the composition is used for the cosmetic purpose such as an improvement of the skin complexion or the like, single administration produces an immediate effect. It is possible to enhance the cosmetic efficacy by increasing a time length of application, frequency of application and period for application. As to the partial slimming, satisfactory effect is produced by using the composition once daily for not less than a month, and the effect is enhanced by increasing a time length of application, number of times of application and period for application.
The carbon dioxide-containing viscous composition of the invention does not lose its efficacy for a long period if it is kept in a sealed vessel or the like. In addition, the composition can be used in such a manner that it is prepared before each administration. More specifically, in the case of preparing the carbon dioxide-containing viscous composition of the invention before each administration, the composition may be obtained by, for example, applying or patching a carbonate-containing aqueous viscous composition or a film or sheet of aqueous or porous polymer, followed by applying, patching or inspersing an acid-containing aqueous composition, a film or sheet of aqueous or porous polymer or granules thereon. Further, the carbon dioxide-containing viscous composition of the invention can also be obtained by fixing the granule or the like on a polymer film or polymer sheet of poor permeability using an adhesive, followed by applying the polymer film or polymer sheet over a carbonate-containing aqueous viscous composition or a film or sheet of aqueous or porous polymer. In this case, the closure therapy can be carried out more efficiently. Of course, the same effect is produced when the carbonate and acid are exchanged in the above combinations, and the carbon dioxide-containing viscous composition can be obtained by using a composite granule of carbonate and acid in combination with the aqueous viscous composition. In the preparation before each administration, the carbon dioxide-containing viscous composition is cooled down due to an endothermic reaction associated with the generation of carbon dioxide; therefore, materials to be used for the preparation or the prepared carbon dioxide-containing viscous composition may be warmed up.
The carbon dioxide-containing viscous composition of the present invention is used for treating the injured tissue and mucosa preferably at a pH of 5-8. Pain may be caused if the pH of the composition is 5 or less due to the acidic stimulation, whereas the tissue may be injured if the pH of the composition is 8 or more due to the protein denaturing action of alkali. The composition of the invention is applied to the skin without injury preferably at a pH of 3-9. Side effects such as pain or eruption may be caused if the pH of the composition is 3 or less due to the acidic stimulation to the skin, whereas the tissue may be injured if the pH of the composition is 9 or more due to the protein denaturing action of alkali.
The carbon dioxide-containing viscous composition of the invention have a water content of about 40-99 wt %, preferably about 60-96 wt %.
In the case of producing carbon dioxide using a carbonate and acid, the carbonate may be used in an amount of about 0.01-30 parts by weight and the acid may be used in an amount of about 0.01-30 parts by weight based on 100 parts by weight of the aqueous viscous composition.
The composition of the invention may retain its volume of, with setting a volume of the composition charged in a graduated cylinder immediately after the preparation as 100, typically 30 or more, preferably 50 or more, more preferably 70 or more 2 hours after the preparation.
The carbon dioxide-containing viscous composition of the invention contains carbon dioxide bubbles in an amount of about 1-99 vol %, preferably about 5-90 vol %, more preferably about 10-80 vol % in the use thereof.
The composition of the invention is capable of treating and preventing or ameliorating itching accompanying mucocutaneous diseases or mucocutaneous disorders such as athlete""s foot, insect bite, atopic dermatitis, nummular eczema, xeroderma, seborrheic eczema, urticaria, prurigo, housewives"" eczema, acne vulgaris, impetigo, folliculitis, carbuncle, furunculosis, phlegmon, pyoderma, psoriasis, ichthyosis, palmoplantar keratoderma, lichen, pityriasis, wound, burn, rhagades, erosion and chilblain; mucocutaneous injuries such as decubitus ulcer, wound, burn, angular stomatitis, skin ulcer, rhagades, erosion, chilblain and gangrene; incomplete takes of skin graft, skin flap, etc.; dental diseases such as gingivitis, alveolar pyorrhea, denture ulcer, nigricans gingiva, stomatitis; skin ulcer, cryesthesia and numbness caused by peripheral circulatory disorders such as thromboangitis obliterans, arteriolosclerosis obliterans, diabetic peripheral circulatory disorder and varicosis in lower extremity; musculoskeletal diseases such as chronic rheumatoid arthritis, cervico-omo-brachial syndrome, myalgia, arthralgia and lumbago; nervous system diseases such as neuralgia, polyarthritis and subcute myelo-optic neuropathy; keratoses such as psoriasis, corn, callosity, ichthyosis, palmoplantar keratoderma, lichen and pityriasis; suppurative dermopathies such as acne vulgaris, impetigo, folliculitis, carbuncle, furunculosis, phlegmon, pyoderma and suppurative eczema; constipation caused by hyporeflexia; suppression of hair re-growth after depilation (treatment of unwanted hair); cosmetic troubles in the skin or hair such as freckles, rough skin, faded skin complexion, loss of tension or brilliancy of skin, loss of hair glossiness and the like without causing side effects as well as of slimming a desired part of the body when applied thereto.
The present invention will be described below in more detail with reference to examples. The invention, however, is not limited to the examples. In the tables shown below, the numerals are expressed in terms of xe2x80x9cpart by weightxe2x80x9d, unless otherwise specified.